Comparative incidence and clinical spectrum of Plasmodium knowlesi malaria, a longitudinal study in Sabah, Malaysia has one of the most successful malaria control programs in Southeast Asia, with marked reductions in the incidence of Plasmodium falciparum and P. vivax over recent decades and an aim to eliminate these species by 2020. However, the simian parasite P. knowlesi has emerged as a major cause of human malaria, and we recently reported that in Sabah, east Malaysia, combined notifications of P. knowlesi and the microscopically near-identical P. malariae increased >10-fold between 2004 - 2011. However, microscopic diagnosis of P. knowlesi is known to be problematic, and definitive diagnosis requires molecular methods. Hence, whether the apparent increase in P. knowlesi is due to increased recognition of the species remains uncertain, and the true incidence and trend of knowlesi malaria in Sabah, in comparison to the other human malaria species, has not been determined. P. knowlesi has a 24-hour replication cycle and can result in high parasitemias with consequent complications. Risk of severe disease appears higher than that of falciparum malaria, and fatal cases have been reported. However, many knowledge gaps remain with regards to the epidemiology and clinical features of knowlesi malaria. Large prospective longitudinal studies have not been conducted, and no prospective study has evaluated the clinical features of knowlesi malaria in children, or the occurrence and consequences of knowlesi malaria in pregnancy. In our proposed study we aim to determine the true incidence and trend of knowlesi malaria in Sabah, in comparison to the other human malaria species. This will be achieved through collaboration with the Sabah Public Health Laboratory, and will involve the implementation of state-wide molecular testing of every case of microscopy-diagnosed malaria in Sabah during the 5-year study period. Basic demographic details including pregnancy status will be recorded for all cases. Our second aim is to determine the epidemiology and clinical spectrum of knowlesi malaria at two district hospitals, including changes over time. This will be achieved through the enrolment of every patient admitted with malaria at two district hospitals in northeast Sabah, with detailed epidemiological and clinical details recorded. Our proposed research will provide for the first time accurate information regarding the true incidence of knowlesi malaria in Sabah, and the trend of this species over time in comparison to the other human malaria species. This will inform malaria control programs in Sabah, in addition to informing other countries in Southeast Asia about the potential emergence of knowlesi malaria as P. falciparum and P. vivax are brought under control. In addition, our prospective district-hospital studies will provide crucial information regarding the clinical features of knowlesi malaria in populations that have not been previously well-studied, including children and pregnant women.